Barbara A. Sampson

The West Nile Virus Outbreak of 1999 in New York: The Flushing Hospital Experience

West Nile Virus (WNV) is a mosquito-borne flavivirus, which has been known to cause human infection in Africa, the Middle East, and southwestern Asia. It has also been isolated in Australia and sporadically in Europe but never in the Americas. Clinical features include acute fever, severe myalgias, headache, conjunctivitis, lymphadenopathy, and a roseolar rash. Rarely is encephalitis or meningitis seen. During the month of August 1999, a cluster of 5 patients with fever, confusion, and weakness were admitted to the intensive care unit of the same hospital in New York City. Ultimately 4 of the 5 developed flaccid paralysis and required ventilatory support. Three patients with less-severe cases presented shortly thereafter. With the assistance of the New York City and New York State health departments and the Centers for Disease Control and Prevention, these were documented as the first cases of WNV infection on this continent.

West Nile Encephalitis

Abstract: West Nile virus was identified by immunohistochemistry (IHC) and polymerase chain reaction (PCR) as the etiologic agent in four encephalitis fatalities in New York City in the late summer of 1999. Fever and profound muscle weakness were the predominant symptoms. Autopsy disclosed encephalitis in two instances and meningoencephalitis in the remaining two. The inflammation was mostly mononuclear and formed microglial nodules and perivascular clusters in the white and gray matter. The brain stem, particularly the medulla, was involved most extensively. In two brains, cranial nerve roots had endoneural mononuclear inflammtion. In addition, one person had acute pancreatitis. On the basis of our experience, we offer recommendations for the autopsy evaluation of suspected WNV fatalities.

The negative autopsy: Sudden cardiac death or other?

One of the most frustrating challenges faced by the forensic pathologist is the inability to determine the cause of death in a young person previously thought healthy. The four steps in the investigation of a sudden death include obtaining the history and scene information, performing a gross and microscopic autopsy, performing appropriate laboratory tests, and making the diagnosis. When examining the heart grossly it is important to preserve the anatomic landmarks, section the coronary arteries closely, and recognize lethal abnormalities such as anomalous origin of the coronary arteries. Specimens useful for toxicologic analysis include whole blood, serum, vitreous humor, gastric contents, bile, urine a purple top tube of blood, and frozen myocardium and spleen. Lethal cardiac diseases with minimal or no anatomic findings include Brugada and Gargs syndromes, the long QT syndrome, and Wolff-Parkinson-White (WPW) syndrome. Consultation with other experts, including cardiac pathologists, cardiologists, electrophysiologists, and molecular biologists, may be helpful in determining a cause of death.

Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths

Sudden unexplained deaths (SUD) in apparently healthy individuals, for which the causes of deaths remained undetermined after comprehensive forensic investigations and autopsy, present vexing challenges to medical examiners and coroners. Cardiac channelopathies, a group of inheritable diseases that primarily affect heart rhythm by altering the cardiac conduction system, have been known as one of the likely causes of SUD. Adhering to the recommendations of including molecular diagnostics of cardiac channelopathies in SUD investigation, the Molecular Genetics Laboratory of the New York City (NYC) Office of Chief Medical Examiner (OCME) has been routinely testing for six major channelopathy genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RyR2) since 2008. Presented here are the results of cardiac channelopathy testing in 274 well-characterized autopsy negative SUD cases, all with thorough medicolegal death investigation including complete autopsy by NYC OCME between 2008 and 2012. The cohort consisted of 141 infants (92.9% younger than six-month old) and 133 non-infants (78.2% were between 19 and 58 years old). Among the ethnically diverse cohort, African American infants had the highest risks of SUD, and African American non-infants died at significantly younger age (23.7 years old, mean age-at-death) than those of other ethnicities (30.3 years old, mean age-at-death). A total of 22 previously classified cardiac channelopathy-associated variants and 24 novel putative channelopathy-associated variants were detected among the infants (13.5%) and non-infants (19.5%). Most channelopathy-associated variants involved the SCN5A gene (68.4% in infants, 50% in non-infants). We believe this is the first study assessing the role of cardiac channelopathy genes in a large and demographically diverse SUD population drawn from a single urban medical examiners office in the United States. Our study supports that molecular testing for cardiac channelopathy is a valuable tool in SUD investigations and provides helpful information to medical examiners/coroners seeking cause of death in SUD as well as potentially life-saving information to surviving family members.

Schizophrenia as a cause of death.

Schizophrenia is a chronic disorder that is associated with increased mortality. Although traumatic deaths account for most of this increase, there is also an increased rate of natural deaths in this population. Altered autonomic physiology in this group might contribute to death. To determine if there are schizophrenics in whom, after a complete autopsy, no recognizable cause of death other than schizophrenia is established, the records of the Office of Chief Medical Examiner of the City of New York were reviewed for deaths associated with schizophrenia and a natural manner of death. Six such decedents were identified, and their histories and autopsy results are described. We believe that schizophrenia per se is a potentially lethal disorder. Autonomic irregularities and their interactions with psychotropic drugs deserve further attention.

Molecular diagnostics of cardiovascular diseases in sudden unexplained death

The most challenging type of sudden cardiac death is sudden unexplained death. The etiologies for sudden unexplained death are diverse and not necessarily confined to the cardiovascular system. Nevertheless, certain cardiovascular diseases, particularly cardiac channelopathies and cardiomyopathies, are known to play significant roles in sudden deaths. The purpose of the review is to provide autopsy pathologists with an actionable guide through illuminating the clinically relevant molecular basis of cardiac channelopathies and cardiomyopathies, as well as the changing landscape of molecular diagnostics.

Buprenorphine infrequently found in fatal overdose in New York City

BACKGROUND Buprenorphine is an opioid agonist medication that is both safe and effective in the treatment of opioid use disorders and the prevention of opioid overdoses. Despite this, media coverage has highlighted public concerns about the potential safety consequences of buprenorphine misuse and diversion. To address the possible contribution of buprenorphine to overdose mortality, we systematically tested post mortem blood specimens from decedents who had died of an unintentional drug overdoses in 2013. METHODS We retrospectively tested consecutive drug overdose cases that occurred from June through October 2013. Cases with available blood specimens were tested for buprenorphine and norbuprenorphine using liquid chromatography-tandem mass spectrometry. Toxicology results were linked to death certificates and case files from New York City Vital Statistics and New York City Office of the Chief Medical Examiner. RESULTS Of the 98 unintentional drug overdose fatalities tested, only 2 (2.0%) tested positive for buprenorphine metabolites. All 98 unintentional fatalities involved multiple substances. CONCLUSIONS Buprenorphine was infrequently found in drug overdose deaths in New York City. Since the safety and efficacy of buprenorphine are well documented, and overdoses resulting from buprenorphine treatment or diversion are very rare, facilitating access to buprenorphine treatment is strongly recommended.

The negative autopsy

Abstract One of the most frustrating challenges faced by the forensic pathologist is the inability to determine the cause of death in a young person previously thought healthy. The four steps in the investigation of a sudden death include obtaining the history and scene information, performing a gross and microscopic autopsy, performing appropriate laboratory tests, and making the diagnosis. When examining the heart grossly it is important to preserve the anatomic landmarks, section the coronary arteries closely, and recognize lethal abnormalities such as anomalous origin of the coronary arteries. Specimens useful for toxicologic analysis include whole blood, serum, vitreous humor, gastric contents, bile, urine a purple top tube of blood, and frozen myocardium and spleen. Lethal cardiac diseases with minimal or no anatomic findings include Brugada and Gargs syndromes, the long QT syndrome, and Wolff–Parkinson–White (WPW) syndrome. Consultation with other experts, including cardiac pathologists, cardiologists, electrophysiologists, and molecular biologists, may be helpful in determining a cause of death.

Retained drugs in the gastrointestinal tracts of deceased victims of oral drug overdose.

Abstract Context. The extent of non-absorbed drug burden in the GI tract following overdose is unknown. Patients who present with clinical signs of toxicity may not undergo decontamination due to assumption that the drug has already been completely absorbed and because of limited scientific evidence of benefit for routine GI decontamination in poisoned patients. Objective. The goal of this study was to assess whether people who die of an oral overdose have unabsorbed drug present in the GI tract. The secondary goal was to analyze pharmacologic characteristics of retained drugs when present. Materials and methods. Retrospective review of autopsy reports from 2008 to 2010, whose cause of death was determined as “intoxication” or “overdose, was performed at the Office of Chief Medical Examiner of the City of New York (OCME NYC).” Decedents of all ages were identified via electronic OCME database. Inclusion criteria were as follows: 1) cause of death “intoxication” or “overdose” noted by forensic autopsy, 2) ingestion of a solid drug formulation. Results. 92 out of 1038 autopsies (9%) that met inclusion criteria had documentation of retained pill fragments, granules, paste, sludge, slurry, or whole pills in the GI tract. The most common drugs found were opioids and anticholinergics. Ninety-eight percent (98%) of the retained drugs were either modified-release preparations or drugs known to slow GI transit. Most decedents were dead on arrival; there were twelve in-hospital deaths and eleven patients died in the Emergency Department. Bupropion and venlafaxine were responsible for four deaths in those who received medical care. One person died in the ICU following bupropion ingestion. Discussion and conclusion. Overdose of an oral drug that either has modified-release properties or slows GI tract motility may result in substantial unabsorbed drug burden remaining in the GI tract.

Spontaneous cerebellar hemorrhage in children.

Spontaneous cerebellar hemorrhages are a rare but often fatal occurrence in children. Although there are several predisposing factors such as blood dyscrasias or astrocytomas, the most common cause of cerebellar hemorrhage in an otherwise healthy child is the rupture of a vascular malformation. We reviewed the files of the Office of Chief Medical Examiner of the City of New York and found four such instances over a period of less than two years. We present these here and outline the approach the forensic pathologist should take in evaluating such deaths.